The goals of the project are to characterize the pathogenesis, natural history and therapy of herpes simplex virus and varicella-zoster virus infections. Our clinical emphasis has been on genital herpes in normal and immune-impaired patients. Analysis of six years of suppressive acyclovir in patients with frequently recurring herpes have shown the drug to remain effective, to be well tolerated, and to not induce drug resistance. We continue to study the ability of ultraviolet light and other physical and chemical agents to induce recurrent herpes simplex infections in humans. A placebo-controlled trial of acyclovir for blocking, u-v induced reactivation is nearly complete. We also initiated a placebo-controlled trial of acyclovir for suppression of frequent, spontaneously recurring oral herpes. The major thrust of our laboratory effort in this project has been the analysis of herpes simplex latency in human ganglia. We demonstrated HSV-1 latency-associated RNAs in trigeminal ganglia and HSV-2 RNAs in sacral ganglia. During the past year primer extension analyses, sequencing and transfections of CAT constructs were used to further define the structure, kinetics, and regulation of these latency-associated RNAS. A putative "variant" promoter has been identified.